Linked Life Data

11904157

Source:http://linkedlifedata.com/resource/pubmed/id/11904157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2002-3-20
pubmed:abstractText
Cardiac sodium channels have been shown to have a higher sensitivity to local anesthetic agents, such as lidocaine, than the sodium channels of other tissues. To examine if this is also true for mexiletine, we have systematically measured mexiletine sensitivity of the Na channel isoforms, rH1, (mu)1, and rBII, which were transiently expressed in human embryonic kidney (HEK) 293 cells. We confirmed that the cardiac isoform rH1 exhibited the highest sensitivity among the three tested channel isoforms. In rH1, (mu)1, and rBII, the respective IC(50) values were 62, 294, and 308 microM mexiletine, in regard to tonic block, and 18, 54, and 268 microM mexiletine, in relation to use (8 Hz)-dependent block. The relatively high drug sensitivity of rH1 was an invariant finding, irrespective of channel state or whether channels were subjected to infrequent or frequent depolarizing stimuli. Mutating specific amino acids in the skeletal muscle isoform (mu)1 (namely, (mu)1-I433V and (mu)1-S251A) to those of the cardiac isoform at putative binding sites for local anesthetic agents revealed that only one of the point mutations ((mu)1-S251A) has relevance to the high cardiac drug sensitivity, because mexiletine produced significantly more use-dependent and tonic block in (mu)1-S251A than wild-type (mu)1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-5793
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
513
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-41
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Molecular basis for exaggerated sensitivity to mexiletine in the cardiac isoform of the fast Na channel.
pubmed:affiliation
Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, 734-8551, Hiroshima, Japan.
pubmed:publicationType
Journal Article